Prognostic significance of liver metastases as first site of generalisation in patients with breast cancer--a retrospective analysis.

Of 672 patients with metastatic breast cancer, 24 evaluable patients with primary liver metastases were analysed with regard to their prognostic variables and survival. In 50% of these patients, liver metastases were found within the first 8.5 months after the diagnosis of breast cancer. The median survival of 10 months (range 0-60+ months) was extremely unfavourable. The median survival of hormone-receptor-positive patients (11 months) was significantly longer than that of patients with hormone-receptor-negative tumours (4 months) (P = 0.025). Patients with elevated lactate dehydrogenase (LDH), glutamic-oxaloacetic transaminase (GOT) (> 50 U/I), or bilirubin levels at diagnosis had a significantly shorter median survival than patients with normal laboratory parameters (P = 0.001, P = 0.047, and P = 0.056, respectively). This retrospective study confirms the short survival time for breast cancer patients with liver metastases as initial site of relapse. Hormone-receptor status and the laboratory parameters LDH, GOT, and bilirubin were identified as important prognostic factors for survival.

A double-blind randomized-phase II trial comparing immunization with antiidiotype goat antibody vaccine SCV 106 versus unspecific goat antibodies in patients with metastatic colorectal cancer.

This article reports on the first double-blind randomized clinical study with an antiidiotype antibody vaccine in patients with metastatic colorectal carcinoma. The study was performed to determine immunological parameters, efficacy, and tolerability of the vaccine. Forty-two patients with metastatic colorectal cancer were randomly assigned to multiple immunizations with goat IgG antiidiotype vaccine SCV 106 (n = 21) or unspecific goat IgG as controls (n = 21). The antiidiotype vaccine mimicked the 17-1A glycoprotein antigen associated with colorectal cancer. Of the 42 patients entered, 39 were evaluable for efficacy (SCV 106, n = 18; controls, n = 21). Twenty-nine patients raised antibodies to the vaccines (immunological responders, SCV 106, n = 12; controls, n = 17). Only in the SCV 106 group was a significant increase (p = 0.002) of titers with specificity of antitumor antibody 17-1A found. According to the International Union Against Cancer (UICC) criteria no tumor response was observed. However, in the SCV 106 group the relative increase of carcinoembryonic antigen (CEA) levels between entry and observed disease progression was lower (p = 0.03) and disease progression was determined less frequently by development of new metastases (p = 0.001). On an intention-to-treat basis, the survival time difference between the two groups was not significant. Comparison of immunological responders in both groups revealed a significant survival advantage of the SCV 106-treated patients compared with controls (mean 67 versus 39 weeks; p = 0.01). Immunizations were well tolerated. Vaccination of immunologically responding metastatic colorectal carcinoma patients with SCV 106 leads to slowed disease progression and tumor dissemination and significantly prolongs survival time.

Collagenous colitis: a study of the distribution of morphological abnormalities and their histological detection.

In collagenous colitis, the literature is conflicting concerning where in the colon the lesions are most likely to be present and most severe. Conflicting data furthermore shed doubt on the sensitivity of the histological detection of the morphological abnormalities and the threshold criteria for diagnosis. We addressed these questions in 56 patients with collagenous colitis. Two hundred ninety-one coded biopsy specimens were analyzed according to six standardized sites from cecum to rectum. Subepithelial collagen deposits were subjectively graded in hematoxylin and eosin (H&E) sections and quantitatively measured in trichrome-stained sections, respectively. Semiquantitative grading was also done for inflammatory changes of the lamina propria and abnormalities of the surface and crypt epithelium. The transverse colon yielded the largest percentage of biopsy specimens (83%) interpreted as diagnostic of collagenous colitis and also had the largest percentage of biopsy specimens with inflammatory changes (98%). Biopsy specimens from both the rectosigmoid and the right colon (ascending and cecum) were significantly less likely to be diagnostic (P<.01). Only 66% of specimens obtained from the rectosigmoid were diagnostic, and 18% of these were interpreted as normal. Subepithelial collagen deposits proved to be significantly thicker in the transverse (median, 46.8 microm; range, 12 to 212.4) and descending (median, 49.2 microm; range, 6 to 230.4) than in the rectosigmoid (median, 33.6 microm; range, 9.6 to 178.8) and right colon (median, 35.4 microm; range, 6 to 140.4), respectively (P<.01). Almost all biopsy specimens (97%) had collagen deposits thicker than 10 microm. However, the subjective interpretation "diagnostic of collagenous colitis" proved to be most consistent with a threshold of 30 microm. Our results indicate that biopsy specimens from at least as proximal as the transverse colon should be obtained to definitely rule out collagenous colitis. Furthermore, it is evident that in a given biopsy specimen, markedly abnormal subepithelial collagen deposition had to be present for an unequivocal histological diagnosis of collagenous colitis.

Low-intensity laser irradiation improves skin circulation in patients with diabetic microangiopathy.

OBJECTIVE: Diabetic foot problems due to angiopathy and neuropathy account for 50% of all nontraumatic amputations and constitute a significant economic burden to society. Low-intensity laser irradiation has been shown to induce wound healing in conditions of reduced microcirculation. We investigated the influence of low-intensity laser irradiation by means of infrared thermography on skin blood circulation in diabetic patients with diabetic microangiopathy. RESEARCH DESIGN AND METHODS: Thirty consecutive patients with diabetic ulcers or gangrenes and elevated levels of glycosylated hemoglobin were randomized by blocks of two to receive either a single low-intensity laser irradiation with an energy density of 30 J/cm2 or a sham irradiation over both forefoot regions in a double-blind placebo-controlled clinical study. Skin blood circulation as indicated by temperature recordings over the forefoot region was detected by infrared thermography. RESULTS: After a single transcutaneous low-intensity laser irradiation, a statistically significant rise in skin temperature was noted (P < 0.001 by ANOVA for repeated measurements), whereas in the sham-irradiated control group, a slight but significant drop in temperature (P < 0.001) was found. Subsequently performed contrasts for comparison of measurements before and after irradiation revealed significant temperature increases at 20 min of irradiation time (P < 0.001), at the end of the irradiation (P < 0.001), and 15 min after stopping the irradiation (P < 0.001). In the sham-irradiated feet, the drop in local skin temperature was not significant at 20 min (P = 0.1), but reached significance at the end of the sham-irradiation procedure (P < 0.001) and 15 min after the end of sham irradiation (P < 0.001). CONCLUSIONS: The data from this first randomized double-blind placebo-controlled clinical trial demonstrate an increase in skin microcirculation due to athermic laser irradiation in patients with diabetic microangiopathy.

Biliary Wallstent endoprosthesis in malignant hilar obstruction: long-term results with regard to the type of obstruction.

AIM: To evaluate the clinical efficacy of percutaneously placed biliary Wallstents in the management of malignant hilar obstruction with regard to the obstruction type. PATIENTS AND METHODS: Sixty-six Wallstents were inserted in 41 patients with inoperable hilar obstruction: 13 patients had a type I obstruction according to Bismuth-classification, 18 a type II, eight a type III, and two a type IV obstruction, respectively. Clinical follow-up data were obtained from all the patients and the referring physicians. RESULTS: Stent placement was technically successfully in all patients. The procedure-related death rate was 2% (one patient), but the overall 30-day mortality rate was 39%, mostly due to advanced malignant disease, cardiac failure or pneumonia. Stent occlusion was found in 11 patients (27%) after 87 days (mean; range, 8-190 days). After stent placement, the mean stent patency was 96 days and the mean survival was 131 days with no significant difference between patients with obstruction type I, II and III. Multivariate analysis revealed that patients with obstruction due to gallbladder carcinoma had a significantly shorter survival than patients with cholangio-carcinoma or hilar obstruction due to metastases. CONCLUSION: Overall, the insertion of Wallstent endoprostheses offers moderate results for palliation of hilar biliary obstruction regardless of the type of obstruction. In patients with cholangiocarcinoma, long-term results are good even for complicated strictures (type III). In patients with hilar obstruction due to gallbladder carcinoma the outcome is generally poor, regardless of the type of obstruction.

Common bile duct obstruction due to malignancy: treatment with plastic versus metal stents.

PURPOSE: To compare the clinical efficacy and treatment costs of plastic versus metal biliary stents. MATERIALS AND METHODS: In a randomized trial, 101 patients with malignant common bile duct obstruction underwent transhepatic stent implantation and were followed up until death. Patients were stratified into risk and nonrisk groups. Forty-nine patients received 12-F plastic stents, and 52 received expandable metal stents. Plastic endoprostheses were placed in a two-step procedure; metal stent, in a single procedure. Kaplan-Meier analyses were used to compare patient survival and stent patency rates. RESULTS: The 30-day mortality rate was significantly lower for metal stents (five of 52 [10%]) than plastic stents (12 of 49 [24%]; P = .05). The obstruction rate was 19% (10 of 52; median patency, 272 days) for metal stents and 27% for plastic stents (13 of 49; median patency, 96 days; P < .01). Median time until death or obstruction was longer for metal stents (122 vs 81 days; P < .01). Placement of metal stents was associated with shorter hospital stay (10 vs 21 days; P < .01) and lower cost ($7,542 vs $12,129; P < .01). CONCLUSION: Use of self-expanding metal stents appears to show substantial benefits for patients and to be cost-effective.

Neoadjuvant chemotherapy (MVAC) in locally invasive bladder cancer.

In order to evaluate the efficacy of neoadjuvant chemotherapy in invasive urothelial carcinoma of the bladder a retrospective analysis was performed. 54 patients without distant metastases (T2-T3b, N0-X, M0) received 3 cycles of neoadjuvant chemotherapy according to the MVAC protocol (methotrexate, vinblastine, doxorubicin and cisplatin) after transurethral resection (TUR) followed by cystectomy. 52 patients had previously undergone cystectomy immediately after TUR. Complete histopathological remission was observed in 9 patients (17.3%) after TUR and in 17 patients (31.5%) after TUR+MVAC. Neoadjuvant MVAC resulted, therefore, in a 14% higher rate of complete remissions. The overall response to TUR was significantly improved by MVAC therapy. Downstaging by neoadjuvant chemotherapy was more readily achieved in initially low-stage tumours (T2: 44.4% and 30.8%, T3a: 47.1% and 19%, T3b: 5.3% and 5.5% in patients receiving TUR+MVAC and TUR alone, respectively). Overall survival did not differ significantly between both groups. Patients who were successfully downstaged to pT0 had a significantly better prognosis, and patients resistant to chemotherapy had the poorest prognosis, showing the shortest survival. In conclusion, histopathological response at cystectomy was improved by neoadjuvant MVAC chemotherapy after TUR and can be expected to be prognostically relevant in those patients who can be downstaged to T0, although overall survival failed to be significantly increased in this relatively small patient sample.

Adjuvant intravesical mitoxantrone after transurethral resection of primary superficial transitional cell carcinoma of the bladder. A prospective randomised study.

A prospective randomised controlled clinical trial began in 1989 on 126 patients with superficial transitional cell carcinoma of the bladder (pTa-pT1, grades 1-3) to compare the efficacy of adjuvant topical mitoxantrone after transurethral resection versus no further treatment. 62 patients received no further treatment, 64 patients received weekly 20 mg mitoxantrone intravesically for 6 weeks after differentiated TUR of all visible tumours. The endpoint of the study was any progression of stage or grade or further recurrences. The median follow up was 29 months--the minimum follow up was 24 months. The percentage of recurrences (25.8 versus 23.4), the recurrence rate (1.2 versus 0.9), the overall disease free interval and the tumour progression rate showed no statistically significant differences (P > 0.05 Mantel-Cox test). Only the comparison of time to recurrence in tumours with recurrences showed a statistically significant difference, with a longer disease free interval for the TUR plus mitoxantrone group (P = 0.016 Mantel-Cox test).

[Topical immunotherapy (KLH) vs. chemotherapy (Ethoglucid) in prevention of recurrence of superficial bladder cancer. A prospective randomized study]. / Topische Immuntherapie (KLH) vs. Chemotherapie (Ethoglucid) in der Rezidivprophylaxe oberflächlicher Harnblasenkarzinome. Eine prospektiv randomisierte Studie.

A prospective randomized controlled study on the effect of KLH (keyhole limpet hemocyanin) versus etoglucid in the prevention of recurrences in primary and recurrent superficial transitional cell carcinoma of the bladder (stage pTa-pT1, grades 1-3 according to the recommendations of UICC and WHO) after complete transurethral resection of the tumor started in 198. Patients in group 1 (n = 76) were immunized with 1 mg KLH intracutaneously, after which they received bladder instillations of 30 mg (30 ml) KLH weekly for 6 weeks and then monthly for 1 year. Patients in group 2 (n = 85) received weekly bladder instillations of 0.565 g etoglucid (50 ml 1% solution) for 6 weeks and then monthly for 1 year. The percentage of recurrences, recurrence rate, disease-free interval and tumor progression rate were evaluated for both treatment groups. The end-point of the study was progression in stage or grade or more than two recurrences during the observation period. The shortest follow-up was 12 months, the mean follow-up, 27.5 months. No statistically significant differences were found between the two groups in percentage of recurrences (43.4% KLH-53.9% etoglucid), recurrence rate (4.4 KLH-3.9 etoglucid), mean disease-free interval (12.1 months KLH-13.6 months etoglucid) or progression rate (6.5% KLH-9.4% etoglucid).

Interferon-alpha stimulates the hypothalamic-pituitary-adrenal axis in vivo and in vitro.

The successful therapeutic use of interferon-alpha (IFN-alpha) in myeloproliferative disorders offered the possibility to test its acute and long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis in humans. ACTH and cortisol plasma concentrations were measured in 8 patients hourly starting from 4 p.m. through 12 p.m. on three occasions. The first time all patients were studied before initiation of therapy, when the vehicle was injected alone. The patients were studied again on day 1 of IFN-alpha therapy (5 million units) and once more after 3 weeks of therapy. On the control day, plasma concentrations of ACTH and cortisol were in the range expected for this time of day. In contrast, after the first administration of IFN-alpha a significant stimulation of the HPA axis was observed. After 3 weeks of IFN-alpha therapy, no significant stimulation of the HPA axis occurred after administration of IFN-alpha. IFN-alpha-induced adaptive changes in the HPA axis were also indicated by a significantly enhanced ACTH and cortisol response to exogenously administered supramaximal doses of corticotropin-releasing hormone (CRH) when the patients had been on IFN-alpha treatment for 3 weeks. To determine the exact locus of the IFN-alpha action, in vitro experiments were performed using rat hypothalamic organ and primary pituitary and adrenal cell culture systems. Thereby a significant stimulation of hypothalamic CRH secretion and rat adrenal corticosterone production was observed after INF-alpha at concentrations of 5 x 10(-8) M or 10(-7) M respectively. In contrast, no direct IFN-alpha effect on pituitary ACTH secretion could be observed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of carotid endarterectomy on various neuropsychologic parameters. A neuropsychologic longitudinal study]. / Einflüsse der Karotisendarterektomie auf verschiedene Hirnleistungsparameter. Eine neuropsychologische Längsschnittstudie.

Carotid endarterectomy was performed in 25 patients with symptomatic cerebrovascular disease. All patients underwent detailed neuropsychological investigations immediately before surgery, immediately after surgery, and again after a follow-up period of 14 months. Immediately after surgery the flicker fusion frequency was temporarily reduced, indicating an impairment of global cognitive functioning. Postoperatively, verbal attention was found to be improved, particularly in younger patients, in patients with TIA, and in patients with left-sided operation. Finally, visual retention (Benton) was improved at the end of the observation period, especially in older patients and in patients with left-sided operation. Considering the complexity of pathologic brain perfusion, the effects of carotid endarterectomy can only be explained if a multidimensional approach is adopted.

Thyroid autoimmunity and hypothyroidism during long-term treatment with recombinant interferon-alpha.

Forty-five patients with myeloproliferative or myelodysplastic syndromes, treated with recombinant interferon-alpha (rIFN-alpha) for a minimum of 1 up to 4 years, were examined for the occurrence of thyroid autoimmunity. During treatment, the rate of thyroid autoimmunity rose to more than 20%. The decrease in severity and frequency of thyroid autoimmunity after withdrawal of IFN shows that this is a potentially reversible side effect. The key determinant for the manifestation of this IFN-related autoimmune phenomenon seems to be a predisposition for autoimmunity, since patients with initially detectable thyroid antibodies are prone to exacerbations of thyroid autoimmunity. Concurrent with thyroid autoimmunity, hypothyroidism occurred but did not correlate with the levels of thyroid antibodies, although severe hypothyroidism in two patients was accompanied by increased levels of thyroid antibodies. This investigation shows that thyroid autoimmunity and consecutively hypothyroidism must be expected in certain patients treated with rIFN-alpha during long periods. Furthermore, it may be assumed that IFN-alpha does not induce the development of autoimmunity, but rather enhances the levels of pre-existent thyroid antibodies.

[Transrectal sonographic (TRUS) prostatic volumetry in assessing tumor response to radiation]. / Transrektal sonographische (TRUS-) Prostatavolumetrie zur Beurteilung des Tumoransprechens auf Radiatio.

The aim of this study was to document the grading-related response of carcinoma of the prostate to radiotherapy, especially in views of the fact that the PSA values of hormonal therapy are not evaluable if hormonal therapy is done prior to radiotherapy or in patients with high likelihood of metastatic spread. Controls were done on 55 patients before, during and after primary external radiotherapy of carcinoma of the prostate with volumetric analysis of transrectal ultrasound (TRUS) of the prostate. There were significant differences between G1 and G2 tumors on the one hand and G3 tumors on the other hand. The latter had a much larger volume to start with and their volume reduced more rapidly after therapy.

MDR1 gene expression and treatment outcome in acute myeloid leukemia.

To prospectively assess the role of MDR1 gene expression in patients with de novo acute myeloid leukemia (AML), levels of MDR1 RNA in blast cells were determined at diagnosis and correlated with treatment outcome in 63 patients. MDR1 RNA levels were negative in 29% and positive in 71% of the patients. The complete remission rate in response to induction chemotherapy was 89% for MDR1 RNA-negative patients and 53% for MDR1 RNA-positive patients (P = .008). Expression of the MDR1 gene was observed in most patients who died early or had resistant disease. Kaplan-Meier curves revealed a decrease in both disease-free survival and overall survival of patients with detectable MDR1 gene expression compared with the disease-free survival and overall survival of MDR1 RNA-negative patients (P = .029 and P = .009, respectively). These data indicate that MDR1 gene expression is an unfavorable prognostic factor and suggest that multidrug resistance is important in AML.

Duplex Doppler sonography in renal parenchymal disease. Histopathologic correlation.

To evaluate the histopathologic changes influencing Doppler measurements of the resistive index (RI) in renal arteries in renal parenchymal diseases, 68 kidneys in 34 consecutive patients with various forms of renal parenchymal diseases were studied by duplex Doppler ultrasound (duplex US) immediately before percutaneous renal biopsy. The RI, renal length, and renal cortical echogenicity were correlated with the amount of glomerular, interstitial, and vascular changes graded on a scale from 0 to 100. The renal vascular resistance and therefore the RI are significantly correlated with the prevalence of arteriolosclerosis, glomerular sclerosis, arteriosclerosis, edema, and focal interstitial fibrosis. There was no significant difference of the RI in five groups of different renal parenchymal diseases. Of 34 patients, 24 presented with an RI less than 0.7, which was thought to be within the normal range so far. Additionally, the RI increases as the patient's age increases, due to higher incidence of arteriosclerosis. Of our patients, 44% presented with normal cortical echogenicity. Quantitative duplex US using the RI does not reliably distinguish different types of renal medical disorders.

[5-Fluorouracil (5-FU)/leucovorin in comparison to other current chemotherapy protocols in metastasizing colorectal carcinoma]. / 5-Fluorouracil(5-FU)/Leucovorin im Vergleich zu anderen aktuellen Chemotherapieschemata beim metastasierten kolorektalen Karzinom.

17 patients with metastasizing colorectal cancer were treated in a phase II-study with systemic intravenous chemotherapy (Petrelli N, Proc ASCO 286, 1987) consisting of leucovorin 500 mg/m2 in a 2 hr infusion and 5-fluorouracil (5-FU) 600 mg/m2 bolus one hour after the commencement of the leucovorin infusion. Limiting toxicities were gastrointestinal, in form of nausea/vomiting of WHO grade 3 (n = 1) and of diarrhoea of maximal grade 4 (n = 5), as well as haematological with a maximal nadir of leucocytes of WHO grade 4 (n = 1) and of thrombocytes of WHO grade 1 (n = 1). Of the 14 evaluable patients an objective response was achieved in 21% of cases (CR: n = 1, PR: n = 2). 64% of the patients showed no change and 14% showed progression of their disease, 7 out of the 17 patients have died; the median survival was 24 months. With respect to objective remission, our result of 21% response rate is lower than the median of 32% of 24 different studies comprising 695 patients; nevertheless, the present response rate is within the range observed in the published studies of between 0% and 67%. In order to estimate the antitumoral efficacy of the new regimen 5-FU/leucovorin more objectively, a retrospective comparison of the therapy regimens used most frequently in disseminated colorectal cancer (5-FU monotherapy, 5-FU/methotrexate (MTX), 5-FU/MTX/low dose leucovorin, 5-FU/cisplatin, 5-FU/leucovorin) has been performed. The continuous administration of 5-FU monotherapy, with an objective response rate of 26%, was superior to standard 5-FU monotherapy as a bolus injection or short-term infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors affecting survival in primary superficial bladder cancer.

In a retrospective study of 345 patients with primary superficial transitional cell carcinoma of the bladder, factors present at the time of initial evaluation and which affect survival were identified. All patients were treated initially by transurethral resection with separate resection of the tumor base and margin. 89 patients received no further treatment after resection of the tumor, 256 patients received adjuvant topical instillation therapy over a period of 6 weeks. The distribution of risk factors in both groups was comparable; the survival rate after 5 years showed no significant difference. The tumor-related mortality rate was 12.5%. The Cox regression model showed carcinoma in situ in the tumor margin and the absence of a tumor-associated tissue inflammatory reaction to be the most important risk factors. Beside these associated risk factors, poor differentiation of the tumor parameter was the most important prognostic factor.

[Prevention of thromboembolism in accident surgery--angiospastic complications with DHE-heparin. A multicenter study]. / Thromboembolieprophylaxe in der Unfallchirurgie--angiospastische Komplikationen bei DHE-Heparin. Eine multizentrische Erhebung.

In immobilized patients different drugs are used for thromboembolism prophylaxis. Arterial vasospastic complications have recently been reported after Heparin-DHE. In our clinical observation five of these cases were treated. A multicenter study was performed in 82 Austrian trauma units investigating the incidence and outcome of complications of Heparin DHE prophylaxis. 147,290 patients had different drugs for thromboembolism prophylaxis. 61,092 got Heparin-DHE. Complications could be observed at 142 patients but only in the group receiving Heparin DHE. 135 cases were treated conservatively (amputation of limbs became necessary in seven patients). In seven other cases immediate operative exposure of the vessels and balloon catheter dilatation was successfully performed. Vasospasm occurred only in patients with Heparin DHE prophylaxis. It is important to realize this possibility, so that early therapeutic measurements can be taken to avoid unnecessary permanent ischaemic damages and limb amputation.

Possible adverse effect of failed adjuvant chemotherapy on the prognosis of women receiving consecutive chemotherapy for recurrent breast cancer.

This study tried to evaluate the impact of adjuvant chemotherapy on the induction of chemoresistance in radically operated upon breast cancer patients. Remission rate, remission duration and survival of a group of women (n = 22) treated with combination chemotherapy (adriamycin and cyclophosphamide, AC) for recurrent breast cancer after failed adjuvant therapy (cyclophosphamide, methotrexate, fluorouracil, vinblastine) were retrospectively compared with the clinical data of non-pre-treated patients (n = 28) receiving the same regimen (AC). The two groups of patients were comparable with regard to their risk factors. In the group of women with prior adjuvant chemotherapy only 3 out of 22 had a partial response, lasting 3, 8, and 16 months; the median survival was 50 months. In the group without prior adjuvant therapy 3 complete and 7 partial remissions with a median remission duration of 15.5 months (range 2-54 months) were found; the median survival was 104 months. The percentage of objective responses among the non-pre-treated patients at 36% was almost significantly higher than that of the pretreated women with 14% (p less than 0.1). Responders to chemotherapy after relapse profited in terms of survival within the first 3 years after radical mastectomy, although no statistically significant difference was observed. The survival data shown assume a "shifting" of women from a group with better prognosis to a group with unfavourable prognosis following failed adjuvant chemotherapy.